This project seeks to identify nervous system diseases associated with the neurotropic viruses herpes simplex types 1 and 2 (HSV-l, -2) and varicella zoster virus (VZV) to examine mechanisms underlying production of neural lesions in experimental models of infection. Problems of particular interest are: (i) the role of infection with HSV, VZV and related neurotropic herpesviruses in the production of CNS and PNS disease, including acute encephalitis and chronic demyelination and (ii) mechanisms of CNS arteritis and stroke induced by neurotropic herpesviruses. During FY 1991, continuing studies of human autopsy tissues to examine nervous system disease caused by VZV showed immunocytochemical evidence of VZV infection in lesions of giant cell arteritis involving the middle cerebral artery near the circle of Willis. In this case, major arteries with cerebral arteritis were ipsilateral to cutaneous lesions of herpes zoster opthalmicus. Studies to examine human tissue sections for viral sequences using polymerase chain reaction technology were initiated. In animal models, a collaborative study of simian varicella virus (SVV) infection, a model for VZV infection, was initiated. This study shows that in sensory ganglia of acutely infected monkeys, SVV can be detected in neurons, satellite and endoneurial cells using immunohistochemical and in situ hybridization methods. Efforts to extend previous observations on HSV-2 reactivations using axotomy to induce HSV reaction in mice showed limited success.